Many food-sourced phytochemicals have strong anticancer activities and can be used as safe anticancer treatment or prevention agents. Many phytochemicals however are lipophilic and are unstable. Although they have strong antioxidant activities and effectively inhibit the proliferation of cancer cells in vitro, the in vivo anticancr activities are typically much lower. Furthermore, despite many delivery systems studied for phytochemicals, few are practical due to limitations in the use of synthetic encapsulation materials, the use of organic solvents and the scalability of processes. The goal of this proposal is to fabricate nanodelivery systems of lipophilic phytochemicals based on food biopolymers for use of functional foods in cancer prevention. In ongoing experiments, dissolving curcumin in a pH 12.0 dairy protein (sodium caseinate) solution and subsequent neutralization using a magnetic stir plate effectively encapsulated curcumin as nanoparticles. The treatments did not cause the degradation of curcumin, and the nanoencapsulated curcumin showed much improved anti-proliferation activity against HCT-116 cells than curcumin pre-dissolved in dimethylsulfoxide. The preliminary data suggest the innovation of low-cost, food grade nanodelivery systems for some lipophilic phytochemicals fabricated with easily scalable processes without the need of specialized equipment, organic solvent, and synthesized/modified materials. Based on the preliminary findings using curcumin, we hypothesize that in vivo anticancer activity of lipophilic phytochemicals can be enhanced by nanoencapsulation in food biopolymers using the above low-cost, low- energy, and organic solvent-free processes. The hypothesis will be tested in two specific aims: 1) conditions of nano-encapsulating lipophilic phytochemicals will be studied using sodium caseinate and two low-viscosity surface-active polysaccharides (gum arabic and soluble soybean polysaccharide) as representative digestible and indigestible food biopolymers. [Casein nanocapsules will be encapsulated in chitosan/calcium pectinate composite microparticles for selective release in the colon.] Curcumin and apigenin will be used as two model lipophilic phytochemicals. Physicochemical properties of nanoparticles, properties related to nanoencapsulation, and in vitro anticancer activities of nanoencapsulated curcumin and apigenin will be characterized using various techniques. 2) in vitro anticancer activities of nano-encapsulated apigenin will be confirmed by in vivo models. The innovation of low-cost, food biopolymer-based nanoencapsulation method addresses the priority of paradigm-shifting approaches to nanomaterials fabrication for cancer applications that could lead, e.g., to improved control of size, shape, surface characteristics, and lower fabrication costs in the previous RFA PA-11- 149. The safe and affordable delivery systems enable the use of phytochemicals as cancer prevention agents in functional foods applications or as cancer curing agents. The elimination of synthetic materials and organic solvents can reduce the side effects and complications for cancer patients with weakened immune systems.